Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis
Los derivados del péptido LL- 37, una catelicidina del sistema inmune han sido ampliamente estudiados por sus efectos antimicrobianos; en el presente estudio se evalúa el efecto antibiopelicula de sus derivados LL37- 1 y DLL-37 diseñados por el grupo de investigación REMA sobre la expresión de algun...
- Autores:
-
Gutierrez Riveros, Sergio Alejandro
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2019
- Institución:
- Colegio Mayor de Cundinamarca
- Repositorio:
- Repositorio Colegio Mayor de Cundinamarca
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- spa
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- https://repositorio.unicolmayor.edu.co/handle/unicolmayor/4769
- Palabra clave:
- Péptido
Investigación
Quorum sensing
Genes
Epidermidis
Aureus
Agentes bactericidas
- Rights
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- License
- Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2019
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Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis |
| title |
Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis |
| spellingShingle |
Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis Péptido Investigación Quorum sensing Genes Epidermidis Aureus Agentes bactericidas |
| title_short |
Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis |
| title_full |
Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis |
| title_fullStr |
Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis |
| title_full_unstemmed |
Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis |
| title_sort |
Efecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. Epidermidis |
| dc.creator.fl_str_mv |
Gutierrez Riveros, Sergio Alejandro |
| dc.contributor.advisor.none.fl_str_mv |
Constanza Muñoz, Liliana |
| dc.contributor.author.none.fl_str_mv |
Gutierrez Riveros, Sergio Alejandro |
| dc.subject.proposal.spa.fl_str_mv |
Péptido Investigación Quorum sensing Genes Epidermidis Aureus Agentes bactericidas |
| topic |
Péptido Investigación Quorum sensing Genes Epidermidis Aureus Agentes bactericidas |
| description |
Los derivados del péptido LL- 37, una catelicidina del sistema inmune han sido ampliamente estudiados por sus efectos antimicrobianos; en el presente estudio se evalúa el efecto antibiopelicula de sus derivados LL37- 1 y DLL-37 diseñados por el grupo de investigación REMA sobre la expresión de algunas proteínas del sistema de Quorum sensing, para ello se evaluó la presencia de algunos genes de complejo agr, se tipificó el AIP por medio de PCR convencional y se realizó un análisis de expresión relativa de los genes del sistema por medio de PCR en tiempo real para aislamientos clínicos de S. aureus y S. epidermidis productores de biopelicula. En cada una de las cepas se encontró al menos uno de los genes del complejo, con lo cual se pudo evidenciar la presencia del sistema en todas las cepas estudiadas, en cuanto al efecto de los péptidos sobre su expresión se observan diferentes efectos individuales para cada una de las cepas que las cepas de S. aureus tienen una disminución de la expresión del gen agrA a las 8 y 10 horas con el péptido LL-37 y las cepas de S. epidermidis a la 10 horas con el péptido DLL-37 para el gen agrB. |
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2019 |
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2019 |
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2022-03-04T17:54:57Z |
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2022-03-04T17:54:57Z |
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Trabajo de grado - Pregrado |
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Weiner L, Webb A, Limbago B, Dudeck M, Patel J, Kallen A et al. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infection Control & Hospital Epidemiology [Internet]. 2016 [cited 15 February 2018]; 37(11):1288-1301. Available from: https://www.cdc.gov/nhsn/pdfs/datastat/2014-AR-data-summary-nhsn.pdf London: Health Protection Agency. Surveillance of Surgical Site Infections in NHS Hospitals in England. Londres; 2012 p. 1- 32. A report from the NNIS System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. American Journal of Infection Control [Internet]. 2004 [cited 16 February 2018]; 32(8):470-485. Available from: https://www.cdc.gov/nhsn/pdfs/datastat/nnis_2004.pdf Grupo Para el Control de la Resistencia Antimicrobiana en Bogotá (GREBO). Resultados de la vigilancia de la resistencia bacteriana año 2016 Componente pediátrico y adulto Análisis de percentiles marcadores de resistencia 2016. Componente pediátrico y adulto. Tendencias de los principales marcadores de resistencia 2008-2016 [Internet]. Bogotá D. C.; 2017. Available from: http://www.grebo.org/documentos/Boletin_Grebo_2017.PDF Hancock R, Sahl H. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nature Biotechnology. 2006; 24(12):1551-1557 Epand R, Vogel H. Diversity of antimicrobial peptides and their mechanisms of action. Biochimica et Biophysica Acta (BBA) – Biomembranes. 1999; 1462(1-2):11-28. Sondi I, Salopek-Sondi B. Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. Journal of Colloid and Interface Science [Internet]. 2004 [cited 29 November 2017]; 275(1):177-182. Available from: https://www.sciencedirect.com/science/article/pii/S0021979704001638 Centers for Disease Controls, ROC (Taiwan). Nosocomial Infections Surveillance System. Available from: https://www.cdc.gov.tw/english/info. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451395/pdf/zcm603.pdf Natsis NE, Cohen PR. Coagulase-Negative Staphylococcus Skin and Soft Tissue Infections. Am J Clin Dermatol. 2018 Jun 7. Doi: 10.1007/s40257-018-0362-9. Kim M, Zhao A, Wang A, Brown Z, Muir T, Stone H et al. Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development. Nature Microbiology [Internet]. 2017 [cited 20 July 2017];2:17080. Available from: https://www.nature.com/articles/nmicrobiol201780 Banerjee G, Ray AK. Quorum-sensing network-associated gene regulation in Gram-positive bacteria. Acta Microbiol Immunol Hung. 2017 Dec 1; 64(4):439-453. Doi: 10.1556/030.64.2017.040 Paulander W, Varming AN, Bojer MS, Friberg C, Bæk K, Ingmer H. The agr quorum sensing system in Staphylococcus aureus cells mediates death of sub-population. BMC Res Notes. 2018 Jul 24;11(1):503. Doi: 10.1186/s13104-018-3600-6. Katherine Y. Le, Michael Otto. Quorum-sensing regulation in staphylococci—an overview. Front Microbiol. 2015; 6: 1174. Published online 2015 Oct 27. Doi: 10.3389/fmicb.2015.01174. Tan L, Li S, Jiang B, Hu X, Li S. Therapeutic Targeting of the Staphylococcus aureus Accessory Gene Regulator (agr) System. Frontiers in Microbiology [Internet]. 2018 [cited 20 August 2018];9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29422887 Geisinger E, Muir T, Novick R. agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides. Proceedings of the National Academy of Sciences [Internet]. 2009 [cited 20 August 2018]; 106(4):1216-1221. Available from: http://www.pnas.org/content/pnas/early/2009/01/15/0807760106.full Thoendel M, Kavanaugh J, Flack C, Horswill A. Peptide Signaling in the Staphylococci. Chemical Reviews [Internet]. 2011 [cited 20 August 2018]; 111(1):117-151. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21174435 Otto M, Süßmuth R, Jung G, Götz F. Structure of the pheromone peptide of theStaphylococcus epidermidis agrsystem. FEBS Letters [Internet]. 1998 [cited 18 January 2018]; 424(1-2):89-94. Available from: https://febs.onlinelibrary.wiley.com/doi/epdf/10.1016/S0014-5793%2898%2900145-8 Saenz HL, Augsburger V, Vuong C, Jack RW, Götz F, Otto M. Inducible expression and cellular location of AgrB, a protein involved in the maturation of the staphylococcal quorum-sensing pheromone. Arch Microbiol. 2000 Dec; 174(6):452-5. Linsheng Zhang, Guangyong Ji. Identification of a Staphylococcal AgrB Segment(s) Responsible for Group-Specific Processing of AgrD by Gene Swapping. J Bacteriol. 2004 Oct; 186(20): 6706–6713. Doi: 10.1128/JB.186.20.6706-6713.2004. Sandeep K. Srivastava, Kalagiri Rajasree, Aneesa Fasim, Gayathri Arakere, Balasubramanian. Influence of the AgrC-AgrA Complex on the Response Time of Staphylococcus aureus Quorum Sensing. J Bacteriol. 2014 Aug; 196(15): 2876–2888. Doi: 10.1128/JB.01530-14. Thoendel M, Horswill AR. Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J Biol Chem. 2009 Aug 14;284(33):21828-38. Doi: 10.1074/jbc.M109.031757 Novick RP1, Geisinger E. Quorum sensing in staphylococci. Send to Annu Rev Genet. 2008; 42:541-64. Doi: 10.1146/annurev.genet.42.110807.091640 Shurko JF, Galega RS, Li C, Lee GC. Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination with vancomycin against S. aureus. J Antibiot (Tokyo). 2018 Aug 17. Doi: 10.1038/s41429-018-0090-7 Gökçınar NB, Karabulut AA, Onaran Z, Yumuşak E, Budak Yıldıran FA. Elevated Tear Human Neutrophil Peptides 1-3, Human Beta Defensin-2 Levels and Conjunctival Cathelicidin LL-37 Gene Expression in Ocular Rosacea. Ocul Immunol Inflamm. 2018 Aug 24:1-10. Doi: 10.1080/09273948.2018.1504971 Sancho-Vaello E. The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions. Front Chem. 2017 Nov 7; 5:86. Doi: 10.3389/fchem.2017.00086 Peerayeh S, Azimian A, Nejad Q, Kashi M. Prevalence of agr Specificity Groups AmongStaphylococcus aureusIsolates From University Hospitals in Tehran. Laboratory Medicine. 2009; 40(1):27-29. Li M. Genetic polymorphism of the accessory gene regulator (agr) locus in Staphylococcus epidermidis and its association with pathogenicity. Journal of Medical Microbiology. 2004; 53(6):545-549. Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction: twenty-something years on. Nature Protocols [Internet]. 2006 [cited 25 April 2018]; 1(2):581-585. Available from: https://www.nature.com/articles/nprot.2006.83. Pfaffl M. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research [Internet]. 2001 [cited 16 July 2018]; 29(9):45e-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11328886 Adhikari R, Arvidson S, Novick R. A Nonsense Mutation in agrA Accounts for the Defect in agr Expression and the Avirulence of Staphylococcus aureus 8325-4 traP::kan. Infection and Immunity [Internet]. 2007 [cited 6 April 2018];75(9):4534-4540. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951176/ Turkey A, Abed J, Suleiman A, Barzani K. Molecular assessment of accessory gene regulator (agr) quorum sensing system in biofilm forming Staphylococcus aureus and study of the effect of silver nanoparticles on agr system. Iran J Microbiol [Internet]. 2018 [cited 14 July 2018];10(1):14- 21. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29922414 Choudhary K, Mih N, Monk J, Kavvas E, Yurkovich J, Sakoulas G et al. The Staphylococcus aureus Two-Component System AgrAC Displays Four Distinct Genomic Arrangements That Delineate Genomic Virulence Factor Signatures. Frontiers in Microbiology [Internet]. 2018 [cited 29 September 2018]; 9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981134/pdf/fmicb-09-01082.pdf van Leeuwen W, van Nieuwenhuizen W, Gijzen C, Verbrugh H, van Belkum A. Population Studies of Methicillin-Resistant and –Sensitive Staphylococcus aureus Strains Reveal a Lack of Variability in the agrD Gene, Encoding a Staphylococcal Autoinducer Peptide. Journal of Bacteriology [Internet]. 2000 [cited 1 August 2018]; 182(20):5721-5729. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11004170 jarraud S. Relationships between Staphylococcus aureus Genetic Background, Virulence Factors, agr Groups (Alleles), and Human Disease. Infection and Immunity [Internet]. 2002 [cited 3 January 2018]; 70(2):631-641. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC127674/pdf/0820.pdf |
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Constanza Muñoz, Liliana14931001657d8307aa3079cad734be46600Gutierrez Riveros, Sergio Alejandroa537af041c52746ef698963ff9948b9f6002022-03-04T17:54:57Z2022-03-04T17:54:57Z2019https://repositorio.unicolmayor.edu.co/handle/unicolmayor/476958684Los derivados del péptido LL- 37, una catelicidina del sistema inmune han sido ampliamente estudiados por sus efectos antimicrobianos; en el presente estudio se evalúa el efecto antibiopelicula de sus derivados LL37- 1 y DLL-37 diseñados por el grupo de investigación REMA sobre la expresión de algunas proteínas del sistema de Quorum sensing, para ello se evaluó la presencia de algunos genes de complejo agr, se tipificó el AIP por medio de PCR convencional y se realizó un análisis de expresión relativa de los genes del sistema por medio de PCR en tiempo real para aislamientos clínicos de S. aureus y S. epidermidis productores de biopelicula. En cada una de las cepas se encontró al menos uno de los genes del complejo, con lo cual se pudo evidenciar la presencia del sistema en todas las cepas estudiadas, en cuanto al efecto de los péptidos sobre su expresión se observan diferentes efectos individuales para cada una de las cepas que las cepas de S. aureus tienen una disminución de la expresión del gen agrA a las 8 y 10 horas con el péptido LL-37 y las cepas de S. epidermidis a la 10 horas con el péptido DLL-37 para el gen agrB.ÍNDICE 2 ÍNDICE DE GRAFICAS 4 ÍNDICE DE TABLAS 6 ÍNDICE DE ANEXOS 7 GRÁFICAS DE ANEXOS 8 TABLAS DE ANEXOS 8 RESUMEN 9 OBJETIVOS 10 INTRODUCCIÓN 11 MARCO TEORICO 13 1. Staphylococcus sp. 13 a. Staphylococcus aureus 13 b. Staphylococcus epidermidis 13 2. Quorum sensing (QS) 14 a. agrA 15 b. agrB 15 c. agrC 16 d. agrD 16 3. Péptido LL-37 17 METODOLOGÍA 18 1. Determinar mediante herramientas de bioinformática los primers para los genes agrA, agrB agrC, agrD que intervienen en el proceso de Quorum sensing en cepas de S. aureus y S. epidermidis. a. Definir las secuencias consenso de cada uno de los genes 18 b. Comprobar de la especificidad de los primers 19 c. Diferenciar los genes autoinductores para QS en las cepas de S. aureus y S. epidermidis 21 2. Identificar los genes del operon agr y los autoinductores que intervienen en el proceso de Quorum sensing en cepas de S. aureus y S. epidermidis. a. Extracción de ADN de los aislamientos de S. aureus y S. epidermidis 22 b. Amplificación de los genes en estudio 22 c. Visualización de los productos de amplificación 23 3. Medir la expresión de los genes agr involucradas en el Quorum sensing en cepas de S. aureus y S. epidermidis en ausencia y presencia de los péptidos LL-37 y DLL-37 a. Extracción de ARN 23 b. Síntesis del cDNA 23 c. Cuantificación de los ácidos nucleicos 23 d. Expresión de los genes 23 e. Análisis estadístico 24 RESULTADOS 25 DISCUSIÓN 36 CONCLUSIÓN 39 BIBLIOGRAFIA 40 ANEXOS 45PregradoBacteriólogo(a) y Laboratorista Clínico51p.application/pdfspaUniversidad Colegio Mayor de CundinamarcaFacultad de Ciencias de la SaludBogotá D.CBacteriología y Laboratorio ClínicoDerechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2019https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/closedAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_14cbEfecto de los péptidos ll-37 sobre la expresión de proteínas del Quorum sensing en cepas de s. Aureus y s. EpidermidisTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/bachelorThesishttps://purl.org/redcol/resource_type/TPinfo:eu-repo/semantics/publishedVersionWeiner L, Webb A, Limbago B, Dudeck M, Patel J, Kallen A et al. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014. Infection Control & Hospital Epidemiology [Internet]. 2016 [cited 15 February 2018]; 37(11):1288-1301. Available from: https://www.cdc.gov/nhsn/pdfs/datastat/2014-AR-data-summary-nhsn.pdfLondon: Health Protection Agency. Surveillance of Surgical Site Infections in NHS Hospitals in England. Londres; 2012 p. 1- 32.A report from the NNIS System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. American Journal of Infection Control [Internet]. 2004 [cited 16 February 2018]; 32(8):470-485. Available from: https://www.cdc.gov/nhsn/pdfs/datastat/nnis_2004.pdfGrupo Para el Control de la Resistencia Antimicrobiana en Bogotá (GREBO). Resultados de la vigilancia de la resistencia bacteriana año 2016 Componente pediátrico y adulto Análisis de percentiles marcadores de resistencia 2016. Componente pediátrico y adulto. Tendencias de los principales marcadores de resistencia 2008-2016 [Internet]. Bogotá D. C.; 2017. Available from: http://www.grebo.org/documentos/Boletin_Grebo_2017.PDFHancock R, Sahl H. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nature Biotechnology. 2006; 24(12):1551-1557Epand R, Vogel H. Diversity of antimicrobial peptides and their mechanisms of action. Biochimica et Biophysica Acta (BBA) – Biomembranes. 1999; 1462(1-2):11-28.Sondi I, Salopek-Sondi B. Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. Journal of Colloid and Interface Science [Internet]. 2004 [cited 29 November 2017]; 275(1):177-182. Available from: https://www.sciencedirect.com/science/article/pii/S0021979704001638Centers for Disease Controls, ROC (Taiwan). Nosocomial Infections Surveillance System. Available from: https://www.cdc.gov.tw/english/info. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451395/pdf/zcm603.pdfNatsis NE, Cohen PR. Coagulase-Negative Staphylococcus Skin and Soft Tissue Infections. Am J Clin Dermatol. 2018 Jun 7. Doi: 10.1007/s40257-018-0362-9.Kim M, Zhao A, Wang A, Brown Z, Muir T, Stone H et al. Surface-attached molecules control Staphylococcus aureus quorum sensing and biofilm development. Nature Microbiology [Internet]. 2017 [cited 20 July 2017];2:17080. Available from: https://www.nature.com/articles/nmicrobiol201780Banerjee G, Ray AK. Quorum-sensing network-associated gene regulation in Gram-positive bacteria. Acta Microbiol Immunol Hung. 2017 Dec 1; 64(4):439-453. Doi: 10.1556/030.64.2017.040Paulander W, Varming AN, Bojer MS, Friberg C, Bæk K, Ingmer H. The agr quorum sensing system in Staphylococcus aureus cells mediates death of sub-population. BMC Res Notes. 2018 Jul 24;11(1):503. Doi: 10.1186/s13104-018-3600-6.Katherine Y. Le, Michael Otto. Quorum-sensing regulation in staphylococci—an overview. Front Microbiol. 2015; 6: 1174. Published online 2015 Oct 27. Doi: 10.3389/fmicb.2015.01174.Tan L, Li S, Jiang B, Hu X, Li S. Therapeutic Targeting of the Staphylococcus aureus Accessory Gene Regulator (agr) System. Frontiers in Microbiology [Internet]. 2018 [cited 20 August 2018];9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29422887Geisinger E, Muir T, Novick R. agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides. Proceedings of the National Academy of Sciences [Internet]. 2009 [cited 20 August 2018]; 106(4):1216-1221. Available from: http://www.pnas.org/content/pnas/early/2009/01/15/0807760106.fullThoendel M, Kavanaugh J, Flack C, Horswill A. Peptide Signaling in the Staphylococci. Chemical Reviews [Internet]. 2011 [cited 20 August 2018]; 111(1):117-151. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21174435Otto M, Süßmuth R, Jung G, Götz F. Structure of the pheromone peptide of theStaphylococcus epidermidis agrsystem. FEBS Letters [Internet]. 1998 [cited 18 January 2018]; 424(1-2):89-94. Available from: https://febs.onlinelibrary.wiley.com/doi/epdf/10.1016/S0014-5793%2898%2900145-8Saenz HL, Augsburger V, Vuong C, Jack RW, Götz F, Otto M. Inducible expression and cellular location of AgrB, a protein involved in the maturation of the staphylococcal quorum-sensing pheromone. Arch Microbiol. 2000 Dec; 174(6):452-5.Linsheng Zhang, Guangyong Ji. Identification of a Staphylococcal AgrB Segment(s) Responsible for Group-Specific Processing of AgrD by Gene Swapping. J Bacteriol. 2004 Oct; 186(20): 6706–6713. Doi: 10.1128/JB.186.20.6706-6713.2004.Sandeep K. Srivastava, Kalagiri Rajasree, Aneesa Fasim, Gayathri Arakere, Balasubramanian. Influence of the AgrC-AgrA Complex on the Response Time of Staphylococcus aureus Quorum Sensing. J Bacteriol. 2014 Aug; 196(15): 2876–2888. Doi: 10.1128/JB.01530-14.Thoendel M, Horswill AR. Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J Biol Chem. 2009 Aug 14;284(33):21828-38. Doi: 10.1074/jbc.M109.031757Novick RP1, Geisinger E. Quorum sensing in staphylococci. Send to Annu Rev Genet. 2008; 42:541-64. Doi: 10.1146/annurev.genet.42.110807.091640Shurko JF, Galega RS, Li C, Lee GC. Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination with vancomycin against S. aureus. J Antibiot (Tokyo). 2018 Aug 17. Doi: 10.1038/s41429-018-0090-7Gökçınar NB, Karabulut AA, Onaran Z, Yumuşak E, Budak Yıldıran FA. Elevated Tear Human Neutrophil Peptides 1-3, Human Beta Defensin-2 Levels and Conjunctival Cathelicidin LL-37 Gene Expression in Ocular Rosacea. Ocul Immunol Inflamm. 2018 Aug 24:1-10. Doi: 10.1080/09273948.2018.1504971Sancho-Vaello E. The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions. Front Chem. 2017 Nov 7; 5:86. Doi: 10.3389/fchem.2017.00086Peerayeh S, Azimian A, Nejad Q, Kashi M. Prevalence of agr Specificity Groups AmongStaphylococcus aureusIsolates From University Hospitals in Tehran. Laboratory Medicine. 2009; 40(1):27-29.Li M. Genetic polymorphism of the accessory gene regulator (agr) locus in Staphylococcus epidermidis and its association with pathogenicity. Journal of Medical Microbiology. 2004; 53(6):545-549.Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction: twenty-something years on. Nature Protocols [Internet]. 2006 [cited 25 April 2018]; 1(2):581-585. Available from: https://www.nature.com/articles/nprot.2006.83.Pfaffl M. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research [Internet]. 2001 [cited 16 July 2018]; 29(9):45e-45. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11328886Adhikari R, Arvidson S, Novick R. A Nonsense Mutation in agrA Accounts for the Defect in agr Expression and the Avirulence of Staphylococcus aureus 8325-4 traP::kan. Infection and Immunity [Internet]. 2007 [cited 6 April 2018];75(9):4534-4540. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951176/Turkey A, Abed J, Suleiman A, Barzani K. Molecular assessment of accessory gene regulator (agr) quorum sensing system in biofilm forming Staphylococcus aureus and study of the effect of silver nanoparticles on agr system. Iran J Microbiol [Internet]. 2018 [cited 14 July 2018];10(1):14- 21. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29922414Choudhary K, Mih N, Monk J, Kavvas E, Yurkovich J, Sakoulas G et al. The Staphylococcus aureus Two-Component System AgrAC Displays Four Distinct Genomic Arrangements That Delineate Genomic Virulence Factor Signatures. Frontiers in Microbiology [Internet]. 2018 [cited 29 September 2018]; 9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981134/pdf/fmicb-09-01082.pdfvan Leeuwen W, van Nieuwenhuizen W, Gijzen C, Verbrugh H, van Belkum A. Population Studies of Methicillin-Resistant and –Sensitive Staphylococcus aureus Strains Reveal a Lack of Variability in the agrD Gene, Encoding a Staphylococcal Autoinducer Peptide. Journal of Bacteriology [Internet]. 2000 [cited 1 August 2018]; 182(20):5721-5729. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11004170jarraud S. Relationships between Staphylococcus aureus Genetic Background, Virulence Factors, agr Groups (Alleles), and Human Disease. Infection and Immunity [Internet]. 2002 [cited 3 January 2018]; 70(2):631-641. 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name.|||https://creativecommons.org/licenses/by-nc-sa/4.0/open accessBiblioteca Digital Unicolmayorrepositorio@unicolmayor.edu.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